The objective os this proposal is to continue a comprehensive research program focussed on study of mechanisms of limbic epilepsy. The proposal brings together investigators with skills in molecular neurobiology, electrophysiology, anatomy, pharmacology, and clinical epilepsy. These molecular neurobiology, electrophysiology, anatomy, pharmacology, and clinical epilepsy. These skills will be focused on tests of alternative hypotheses advanced to explain the hyperexcitability characteristic of limbic epilepsy. These hypotheses will be tested in hippocampal slices isolated from normal rodents and from rodents in which epilepsy has been induced. The work is centered in particular on the excitability of two principal neuronal populations, the dentate granule cells and CA3 pyramidal cells. Successful completion of the work proposed promises to shed light on the mechanisms underlying limbic epilepsy. Such insights will hopefully lead to new and more effective therapies of this disorder. Insights into normal hippocampal circuitry and how it is modified following brain injury and pathologic activity will also emerge from this work; this promises to aid understanding a diversity of nervous system disorders in limbic epilepsy.